Efficacy and Safety of the Administration of Betalactam Antibiotics in Continuous or Extended Infusion Compared to Intermittent Infusion in Patients With Sepsis in Two Pediatric Third-level Care Hospitals
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 426
- 试验地点
- 2
- 主要终点
- Number of Participants With Clinical Response
研究概览
简要总结
This study evaluates the efficacy and safety of the administration of betalactam antibiotics in prolonged infusion compared to intermittent infusion in children with sepsis. Half of participants will receive piperacillin/tazobactam, imipenem or meropenem in continuous or extended infusion, while the other half will receive piperacillin/tazobactam, imipenem or meropenem in intermittent infusion.
详细描述
Sepsis is the leading cause of morbidity and mortality in hospitalised patients globally. Betalactams are time-dependent antibiotics, and so, the duration of time for which the free drug plasma concentration remains above the minimum inhibitory concentration (fT > MIC) is the pharmacokinetic/pharmacodynamic index associated with bacterial killing and clinical improvement. Numerous studies have demonstrated that continuous infusion (infusion in 24 hours) and extended infusion (through prolonging the infusion time to greater than 3 hours) allows the maintenance of concentrations above the MIC for a longer period of time within the dosing interval (30 minute or 1 hour), and so, capitalises on the pharmacodynamic properties of betalactams and maximises bacterial killing, therefore potentially improving clinical outcomes. In adult patients, the several studies suggest that prolonged infusion may offer clinical benefits and significant reduction in mortality without increasing the risk of toxicity, however, there is limited information about these dosing strategies in pediatric patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 1 Month 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with sepsis, who have been evaluated by an infectious physician and are candidates to receive piperacillin/tazobactam, imipenem or meropenem as empiric treatment.
排除标准
- •Patients with a history of allergy to one or more of the proposed antibiotics.
- •Patients with chronic kidney disease or acute renal failure.
- •Patients with acute liver failure of any cause.
- •Patients in palliative or supportive care only.
研究组 & 干预措施
Intermittent Piperacillin/tazobactam
Piperacillin/tazobactam 300mg/kg/day, divided into 4 doses/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 30 minutes infusion every 6 hours.
干预措施: Intermittent Piperacillin/tazobactam (Drug)
Continuous Piperacillin/tazobactam
Piperacillin/tazobactam initial doses 75mg/kg in 30 minutes infusion, immediately thereafter continue 300mg/kg/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 24 hours infusion every 24 hours, as determined by antibiotic stability at room temperature.
干预措施: Continuous Piperacillin/tazobactam (Drug)
Intermittent Imipenem
Imipenem 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes infusion every 6 hours.
干预措施: Intermittent Imipenem (Drug)
Extended Imipenem
Imipenem initial doses 20mg/kg in 60 minutes infusion, immediately thereafter continue 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 6 hours infusion every 6 hours, as determined by antibiotic stability at room temperature.
干预措施: Extended Imipenem (Drug)
Intermittent Meropenem
Meropenem 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes every 8 hours.
干预措施: Intermittent Meropenem (Drug)
Extended Meropenem
Meropenem initial doses 35mg/kg in 60 minutes infusion, immediately thereafter continue 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution at a concentration of 7mg/ml, to be administered in 8 hours infusion every 8 hours, as determined by antibiotic stability at room temperature.
干预措施: Extended Meropenem (Drug)
结局指标
主要结局
Number of Participants With Clinical Response
时间窗: Number of participants with clinical response at 14 days after antibiotic cessation, up to an average of 28 days or the day of your discharge if this occurred before 14 days after antibiotic cessation.
Resolution. Disappearance of all signs and symptoms related to the infection. Failure. Insufficient lessening of the signs and symptoms of infection to qualify as improvement, including death or indeterminate (no evaluation possible, for any reason).
次要结局
- Number of Participants With Adverse Events(Number of participants with adverse events evaluated by an physician at the time of administration of antibiotics, up to an average to 24 hours after the study drug cessation.)
研究者
Yazmín Del Carmen Fuentes Pacheco
Pediatric Infectious Disease
Coordinación de Investigación en Salud, Mexico